najoNanosystems: Physics, Chemistry, MathematicsНаносистемы: физика, химия, математика2220-80542305-7971Университет ИТМО10.17586/2220-8054-2025-16-5-650-659najo-1536Research ArticleCHEMISTRY AND MATERIALS SCIENCEХИМИЯ И НАУКА О МАТЕРИАЛАХControlled release of homogeneous polypeptides from carbon nanotubes with varying PH: molecular dynamics simulationКонтролируемый выход однородных полипептидов из углеродной нанотрубки при изменении водородного показателя: молекулярно-динамическое моделированиеhttps://orcid.org/0000-0002-7960-3482КручининН. Ю.KruchininN. Yu.

Оренбург

Nikita Yu. Kruchinin

Orenburg

kruchinin56@mail.ruОренбургский государственный университет, Центр лазерной и информационной биофизикиOrenburg State University, Center of Laser and Informational Biophysics202505112025165650659Copyright © Kruchinin N.Y., 20252025Кручинин Н.Ю.Kruchinin N.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nanojournal.ifmo.ru/jour/article/view/1536

Using molecular dynamics simulation at different pH levels, changes in the conformations of homogeneous polypeptides located singly or in pairs inside a carbon nanotube were studied. The radial distributions of the density of polypeptide atoms, the distribution of macrochain atoms along the nanotube axis, and the dependences of various components of the potential energy of the nanosystem were calculated. At the isoelectric point, the polypeptides were located in the central part of the carbon nanotube, spreading out along its walls. As the pH level deviated from the isoelectric point, the polypeptide located singly inside the carbon nanotube first unfolded and stretched along its axis, and when almost all links of the macromolecule acquired an electric charge, it exited the nanotube. Polypeptides located in pairs inside the carbon nanotube repelled each other with a change in the pH value and shifted to opposite ends of the nanotube, being released from it.

С использованием молекулярно-динамического моделирования при различных уровнях pH исследованы изменения конформаций однородных полипептидов, которые располагались по одиночке или попарно внутри углеродной нанотрубки. Рассчитаны радиальные распределения плотности атомов полипептида, распределения атомов макроцепи вдоль оси нанотрубки, а также зависимости различных компонентов потенциальной энергии наносистемы. В изоэлектрической точке полипептиды находились в центральной части углеродной нанотрубки, распластываясь по ее стенкам. По мере отклонения уровня pH от изоэлектрической точки одиночно расположенный внутри углеродной нанотрубки полипептид сначала разворачивался и вытягивался вдоль ее оси, а когда почти все звенья макромолекулы приобретали электрический заряд – происходил ее выход из нанотрубки. Попарно расположенные внутри углеродной нанотрубки полипептиды при изменении водородного показателя отталкивались друг от друга и смещались на противоположные концы нанотрубки, высвобождаясь из нее.

молекулярная динамикауглеродная нанотрубкаполипептидводородный показательконформацияконтролируемый выходmolecular dynamicscarbon nanotubepolypeptidepHconformationcontrolled releaseThe study was carried out with the financial support of the Ministry of Science and Higher Education of the Russian Federation within the framework of a grant for conducting large scientific projects in priority areas of scientific and technological development 075-15-2024-550.ReferencesBalasubramanian K., Burghard M. Biosensors based on carbon nanotubes. Anal Bioanal Chem, 2006, 385, P. 452–468.Balasubramanian K., Burghard M. Biosensors based on carbon nanotubes. Anal Bioanal Chem, 2006, 385, P. 452–468.Qi H., Mader E., Liu J. Unique water sensors based on carbon nanotube–cellulose composites. ¨ Sensors and Actuators B: Chemical, 2013, 185, P. 225–230.Qi H., Mader E., Liu J. Unique water sensors based on carbon nanotube–cellulose composites. ¨ Sensors and Actuators B: Chemical, 2013, 185, P. 225–230.Tilmaciu C-M., Morris M.C. Carbon nanotube biosensors. Front. Chem., 2015, 3, P. 59.Tilmaciu C-M., Morris M.C. Carbon nanotube biosensors. Front. Chem., 2015, 3, P. 59.Ferrier D.C., Honeychurch K.C. Carbon nanotube (CNT)-based biosensors. Biosensors, 2021, 11, P. 486.Ferrier D.C., Honeychurch K.C. Carbon nanotube (CNT)-based biosensors. Biosensors, 2021, 11, P. 486.Ranjbari S., Bolourinezhad M., Kesharwani P., Rezayi M, Sahebkar A. Applications of carbon nanotube biosensors: Sensing the future. Journal of Drug Delivery Science and Technology, 2024, 97, P. 105747.Ranjbari S., Bolourinezhad M., Kesharwani P., Rezayi M, Sahebkar A. Applications of carbon nanotube biosensors: Sensing the future. Journal of Drug Delivery Science and Technology, 2024, 97, P. 105747.Dewey H.M., Lamb A., Budhathoki-Uprety J. Recent advances on applications of single-walled carbon nanotubes as cutting-edge optical nanosensors for biosensing technologies. Nanoscale, 2024, 16, P. 16344–16375.Dewey H.M., Lamb A., Budhathoki-Uprety J. Recent advances on applications of single-walled carbon nanotubes as cutting-edge optical nanosensors for biosensing technologies. Nanoscale, 2024, 16, P. 16344–16375.Gazzato L., Frasconi M. Carbon nanotubes and their composites for flexible electrochemical biosensors. Analysis & Sensing, 2025, 5, P. e202400038.Gazzato L., Frasconi M. Carbon nanotubes and their composites for flexible electrochemical biosensors. Analysis & Sensing, 2025, 5, P. e202400038.Bianco A., Kostarelos K., Prato M. Applications of carbon nanotubes in drug delivery. Current Opinion in Chemical Biology, 2005, 9(6), P. 674– 679.Bianco A., Kostarelos K., Prato M. Applications of carbon nanotubes in drug delivery. Current Opinion in Chemical Biology, 2005, 9(6), P. 674– 679.Meng X., Zhang Z., Li L. Micro/nano needles for advanced drug delivery. Progress in Natural Science: Materials International, 2020, 30(5), P. 589–596.Meng X., Zhang Z., Li L. Micro/nano needles for advanced drug delivery. Progress in Natural Science: Materials International, 2020, 30(5), P. 589–596.Alshawwa S.Z., Kassem A.A., Farid R.M., Mostafa S.K., Labib G.S. Nanocarrier drug delivery systems: characterization, limitations, future perspectives and implementation of artificial intelligence. Pharmaceutics, 2022, 14, P. 883.Alshawwa S.Z., Kassem A.A., Farid R.M., Mostafa S.K., Labib G.S. Nanocarrier drug delivery systems: characterization, limitations, future perspectives and implementation of artificial intelligence. Pharmaceutics, 2022, 14, P. 883.Roxbury D., Zhang S., Mittal J., DeGrado W.F., Jagota A. Structural stability and binding strength of a designed peptide-carbon nanotube hybrid. J. Phys. Chem. C, 2013, 117, P. 26255–26261.Roxbury D., Zhang S., Mittal J., DeGrado W.F., Jagota A. Structural stability and binding strength of a designed peptide-carbon nanotube hybrid. J. Phys. Chem. C, 2013, 117, P. 26255–26261.Wang H., Michielssens S., Moors S.L.C., Ceulemans A. Molecular dynamics study of dipalmitoylphosphatidylcholine lipid layer self-assembly onto a single-walled carbon nanotube. Nano Res., 2009, 2, P. 945–954.Wang H., Michielssens S., Moors S.L.C., Ceulemans A. Molecular dynamics study of dipalmitoylphosphatidylcholine lipid layer self-assembly onto a single-walled carbon nanotube. Nano Res., 2009, 2, P. 945–954.Roxbury D., Manohar S., Jagota A. Molecular simulation of DNA β-sheet and β-barrel structures on graphite and carbon nanotubes. J. Phys. Chem. C, 2010, 114, P. 13267–13276.Roxbury D., Manohar S., Jagota A. Molecular simulation of DNA β-sheet and β-barrel structures on graphite and carbon nanotubes. J. Phys. Chem. C, 2010, 114, P. 13267–13276.Li L., Cao Q., Liu H., Qiao X., Gu Z., Yu Y., Zuo C. Understanding interactions between poly(styrene-cosodium styrene sulfonate) and singlewalled carbon nanotubes. J Polym Sci., 2021, 59, P. 182–190.Li L., Cao Q., Liu H., Qiao X., Gu Z., Yu Y., Zuo C. Understanding interactions between poly(styrene-cosodium styrene sulfonate) and singlewalled carbon nanotubes. J Polym Sci., 2021, 59, P. 182–190.Kruchinin N.Yu., Kucherenko M.G. Molecular dynamics simulation of the conformational structure of uniform polypeptides on the surface of a polarized metal prolate nanospheroid with varying pH. Russian Journal of Physical Chemistry A, 2022, 96(3), P. 624–632.Kruchinin N.Yu., Kucherenko M.G. Molecular dynamics simulation of the conformational structure of uniform polypeptides on the surface of a polarized metal prolate nanospheroid with varying pH. Russian Journal of Physical Chemistry A, 2022, 96(3), P. 624–632.Kruchinin N.Yu. Molecular dynamics simulation of the rearrangement of polyampholyte conformations on the surface of a charged oblate metal nanospheroid in a microwave electric field. Nanosystems: Physics, Chemistry, Mathematics, 2023, 14(6), P. 719–728.Kruchinin N.Yu. Molecular dynamics simulation of the rearrangement of polyampholyte conformations on the surface of a charged oblate metal nanospheroid in a microwave electric field. Nanosystems: Physics, Chemistry, Mathematics, 2023, 14(6), P. 719–728.Kruchinin N.Yu., Kucherenko M.G. Conformational structure of a complex of two oppositely charged polyelectrolytes on the surface of a charged spherical metal nanoparticle. High Energy Chemistry, 2024, 58(6), P. 615–623.Kruchinin N.Yu., Kucherenko M.G. Conformational structure of a complex of two oppositely charged polyelectrolytes on the surface of a charged spherical metal nanoparticle. High Energy Chemistry, 2024, 58(6), P. 615–623.Kruchinin N.Yu., Kucherenko M.G. Conformational changes of two oppositely charged polyelectrolytes, including those combined into a single block copolymer, on the surface of a charged or transversely polarized cylindrical metal nanowire. Journal of Polymer Research, 2025, 32(3), P. 79.Kruchinin N.Yu., Kucherenko M.G. Conformational changes of two oppositely charged polyelectrolytes, including those combined into a single block copolymer, on the surface of a charged or transversely polarized cylindrical metal nanowire. Journal of Polymer Research, 2025, 32(3), P. 79.Salimi A., Compton R.G., Hallaj R. Glucose biosensor prepared by glucose oxidase encapsulated sol-gel and carbon-nanotube-modified basal plane pyrolytic graphite electrode. Anal Biochem, 2004, 333(1), P. 49–56.Salimi A., Compton R.G., Hallaj R. Glucose biosensor prepared by glucose oxidase encapsulated sol-gel and carbon-nanotube-modified basal plane pyrolytic graphite electrode. Anal Biochem, 2004, 333(1), P. 49–56.Chen Q., Wang Q., Liu Y.-C., Wu T., Kang Y., Moore J.D. Gubbins K. E. Energetics investigation on encapsulation of protein/peptide drugs in carbon nanotubes. The Journal of Chemical Physics, 2009, 131(1), P. 015101.Chen Q., Wang Q., Liu Y.-C., Wu T., Kang Y., Moore J.D. Gubbins K. E. Energetics investigation on encapsulation of protein/peptide drugs in carbon nanotubes. The Journal of Chemical Physics, 2009, 131(1), P. 015101.Kang Y., Wang Q., Liu Y.-C., Wu T., Chen Q., Guan W.-J. Dynamic mechanism of collagen-like peptide encapsulated into carbon nanotubes. The Journal of Physical Chemistry B, 2008, 112(15), P. 4801–4807.Kang Y., Wang Q., Liu Y.-C., Wu T., Chen Q., Guan W.-J. Dynamic mechanism of collagen-like peptide encapsulated into carbon nanotubes. The Journal of Physical Chemistry B, 2008, 112(15), P. 4801–4807.Kang Y., Liu Y.-C., Wang Q., Shen J.-W., Wu T., Guan, W.-J. On the spontaneous encapsulation of proteins in carbon nanotubes. Biomaterials, 2009, 30(14), P. 2807–2815.Kang Y., Liu Y.-C., Wang Q., Shen J.-W., Wu T., Guan, W.-J. On the spontaneous encapsulation of proteins in carbon nanotubes. Biomaterials, 2009, 30(14), P. 2807–2815.Zhang Z., Kang Y., Liang L., Liu Y., Wu T., Wang Q. Peptide encapsulation regulated by the geometry of carbon nanotubes. Biomaterials, 2014, 35(5), P. 1771–1778.Zhang Z., Kang Y., Liang L., Liu Y., Wu T., Wang Q. Peptide encapsulation regulated by the geometry of carbon nanotubes. Biomaterials, 2014, 35(5), P. 1771–1778.Yang N., Chen X., Ren T., Zhang P., Yang D. Carbon nanotube based biosensors. Sensors and Actuators B: Chemical, 2015, 207(A), P. 90–715.Yang N., Chen X., Ren T., Zhang P., Yang D. Carbon nanotube based biosensors. Sensors and Actuators B: Chemical, 2015, 207(A), P. 90–715.Chavan K.S., Barton S.C. Confinement and Diffusion of Small Molecules in a Molecular-Scale Tunnel. Journal of The Electrochemical Society, 167, P. 023505.Chavan K.S., Barton S.C. Confinement and Diffusion of Small Molecules in a Molecular-Scale Tunnel. Journal of The Electrochemical Society, 167, P. 023505.Li W., Cheng S., Wang B., Mao Z., Zhang J., Zhang Y., Liu Q.H. The transport of a charged peptide through carbon nanotubes under an external electric field: a molecular dynamics simulation. RSC Adv., 2021, 11, P. 23589–23596.Li W., Cheng S., Wang B., Mao Z., Zhang J., Zhang Y., Liu Q.H. The transport of a charged peptide through carbon nanotubes under an external electric field: a molecular dynamics simulation. RSC Adv., 2021, 11, P. 23589–23596.Chen Q., Liang L., Zhang Z., Wang Q. Release of an encapsulated peptide from carbon nanotubes driven by electric fields: a molecular dynamics study. ACS Omega, 2021, 6(41), P. 27485–27490.Chen Q., Liang L., Zhang Z., Wang Q. Release of an encapsulated peptide from carbon nanotubes driven by electric fields: a molecular dynamics study. ACS Omega, 2021, 6(41), P. 27485–27490.Andrade L.R.M., Andrade L.N., Bahu J.O., Concha V.O.C., Machado A.T., Pires D.S., Santos R., Cardoso T.F.M., Cardoso J.C., Albuquerque- ´ Junior R.L.C., Severino P., Souto E.B. Biomedical applications of carbon nanotubes: A systematic review of data and clinical trials. Journal of Drug Delivery Science and Technology, 2024, 99, P. 105932.Andrade L.R.M., Andrade L.N., Bahu J.O., Concha V.O.C., Machado A.T., Pires D.S., Santos R., Cardoso T.F.M., Cardoso J.C., Albuquerque- ´ Junior R.L.C., Severino P., Souto E.B. Biomedical applications of carbon nanotubes: A systematic review of data and clinical trials. Journal of Drug Delivery Science and Technology, 2024, 99, P. 105932.Batys P., Morga M., Bonarek P., Sammalkorpi M. pH-Induced Changes in Polypeptide Conformation: Force-Field Comparison with Experimental Validation. J. Phys. Chem. B, 2020, 124(14), P. 2961–2972.Batys P., Morga M., Bonarek P., Sammalkorpi M. pH-Induced Changes in Polypeptide Conformation: Force-Field Comparison with Experimental Validation. J. Phys. Chem. B, 2020, 124(14), P. 2961–2972.Resende L.F.T., Basilio F.C., Filho P.A., Therezio E.M., Silva R.A., Oliveira O.N., Marletta A., Campana P.T. Revisiting the conformational ´ transition model for the pH dependence of BSA structure using photoluminescence, circular dichroism, and ellipsometric Raman spectroscopy. International Journal of Biological Macromolecules, 2024, 259(1), P. 129142.Resende L.F.T., Basilio F.C., Filho P.A., Therezio E.M., Silva R.A., Oliveira O.N., Marletta A., Campana P.T. Revisiting the conformational ´ transition model for the pH dependence of BSA structure using photoluminescence, circular dichroism, and ellipsometric Raman spectroscopy. International Journal of Biological Macromolecules, 2024, 259(1), P. 129142.Stepanenko D., Wang Y., Simmerling C. Assessing pH-Dependent Conformational Changes in the Fusion Peptide Proximal Region of the SARSCoV-2 Spike Glycoprotein. Viruses, 2024, 16, P. 1066.Stepanenko D., Wang Y., Simmerling C. Assessing pH-Dependent Conformational Changes in the Fusion Peptide Proximal Region of the SARSCoV-2 Spike Glycoprotein. Viruses, 2024, 16, P. 1066.Phillips J.C., Braun R., Wang W., Gumbart J., Tajkhorshid E., Villa E., Chipot C., Skeel R.D., Kale L., Schulten K. Scalable molecular dynamics ´ with NAMD. J Comput Chem., 2005, 26, P. 1781–1802.Phillips J.C., Braun R., Wang W., Gumbart J., Tajkhorshid E., Villa E., Chipot C., Skeel R.D., Kale L., Schulten K. Scalable molecular dynamics ´ with NAMD. J Comput Chem., 2005, 26, P. 1781–1802.MacKerell Jr. A.D., Bashford D., Bellott M., Dunbrack Jr. R.L., Evanseck J.D., Field M.J., Fischer S., Gao J., Guo H., Ha S., Joseph-McCarthy D., Kuchnir L., Kuczera K., Lau F.T.K., Mattos C., Michnick S., Ngo T., Nguyen D.T., Prodhom B., Reiher W.E., Roux B., Schlenkrich M., Smith J.C., Stote R., Straub J., Watanabe M., Wiorkiewicz-Kuczera J., Yin D., Karplus M. All-atom empirical potential for molecular modeling and ´ dynamics studies of proteins. J. Phys. Chem. B., 1998, 102(18), P. 3586–3616.MacKerell Jr. A.D., Bashford D., Bellott M., Dunbrack Jr. R.L., Evanseck J.D., Field M.J., Fischer S., Gao J., Guo H., Ha S., Joseph-McCarthy D., Kuchnir L., Kuczera K., Lau F.T.K., Mattos C., Michnick S., Ngo T., Nguyen D.T., Prodhom B., Reiher W.E., Roux B., Schlenkrich M., Smith J.C., Stote R., Straub J., Watanabe M., Wiorkiewicz-Kuczera J., Yin D., Karplus M. All-atom empirical potential for molecular modeling and ´ dynamics studies of proteins. J. Phys. Chem. B., 1998, 102(18), P. 3586–3616.Huang J., Rauscher S., Nawrocki G., Ran T., Feig M., de Groot B.L., Grubmuller H., MacKerell Jr. A.D. CHARMM36m: an improved force field ¨ for folded and intrinsically dis-ordered proteins. Nature Methods, 2016, 14, P. 71–73.Huang J., Rauscher S., Nawrocki G., Ran T., Feig M., de Groot B.L., Grubmuller H., MacKerell Jr. A.D. CHARMM36m: an improved force field ¨ for folded and intrinsically dis-ordered proteins. Nature Methods, 2016, 14, P. 71–73.Radak B.K., Chipot C., Suh D., Jo S., Jiang W., Phillips J.C., Schulten K., Roux B. Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems. J. Chem. Theory Comput., 2017, 13(12), P. 5933–5944.Radak B.K., Chipot C., Suh D., Jo S., Jiang W., Phillips J.C., Schulten K., Roux B. Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems. J. Chem. Theory Comput., 2017, 13(12), P. 5933–5944.Zhu F, Schulten K. Water and Proton Conduction through Carbon Nanotubes as Models for Biological Channels. Biophysical Journal, 2003, 85(1), P. 236–244.Zhu F, Schulten K. Water and Proton Conduction through Carbon Nanotubes as Models for Biological Channels. Biophysical Journal, 2003, 85(1), P. 236–244.Darden T., York D., Pedersen L. Particle mesh Ewald: An N·log(N) method for Ewald sums in large systems. J. Chem. Phys., 1993, 98, P. 10089– 10092.Darden T., York D., Pedersen L. Particle mesh Ewald: An N·log(N) method for Ewald sums in large systems. J. Chem. Phys., 1993, 98, P. 10089– 10092.Jorgensen W.L., Chandrasekhar J., Madura J.D., Impey R.W., Klein M.L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys., 1983, 79, P. 926–935.Jorgensen W.L., Chandrasekhar J., Madura J.D., Impey R.W., Klein M.L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys., 1983, 79, P. 926–935.Kucherenko M.G., Rusinov A.P., Chmereva T.M., Ignat’ev A.A., Kislov D.A., Kruchinin N.Yu. Kinetics of photoreactions in a regular porous nanostructure with cylindrical cells filled with activator-containing macromolecules. Optics and Spectroscopy, 2009, 107(3), P. 480–485.Kucherenko M.G., Rusinov A.P., Chmereva T.M., Ignat’ev A.A., Kislov D.A., Kruchinin N.Yu. Kinetics of photoreactions in a regular porous nanostructure with cylindrical cells filled with activator-containing macromolecules. Optics and Spectroscopy, 2009, 107(3), P. 480–485.

The authors declare that there are no conflicts of interest present.